高密度脂蛋白治疗冠心病的初步观察

<正> 冠状动脉内壁形成以胆固醇为主的脂肪斑块为冠心病的特征。人血高密度脂蛋白能促进实验性动脉粥样硬化家兔血管内壁的脂肪斑块消退(张兴义等:生物制品学杂志:3(1):10,1990)。试用人血高密度脂蛋白治疗冠心病患者,也获得了预期的效果。选择的对象为208医院的住院患者26人,其中稳定劳累型心绞痛19例,无症状心肌缺血6例,梗塞后心绞痛1例。男24例,女2例。年龄为45～79岁,平均为67岁、冠心病史为5～22年,平均12.8     

可以治疗血管疾病的磁导基因疗法——纳米新技术快速修复小鼠动脉内衬血管壁

正心血管疾病每年使数百万人的生命处于危险之中,而结合基因疗法和磁体技术的新技术在未来有可能会为患者提供新的治疗手段。研究人员已经制备出携带与正常基因连接在一起的磁性纳米颗粒的细胞,可以利用外部磁场改变细胞的方位,并利用它们修复小鼠受损的动脉。动脉阻塞可引发心脏病或中风。动脉中平滑的内衬血管壁因老化或高胆固醇等疾病而受到损坏时,斑块在内壁上会不断增长,     

球囊损伤加高脂喂养建立大鼠髂动脉粥样硬化模型

目的探索建立髂动脉粥样硬化动物模型的有效方法。方法将Wistar大鼠18只,雌雄各半,随机分为三组:高脂(加VD3) 球囊损伤组、高脂组、正常喂养组。在实验第90天检测血清总胆固醇、甘油三酯,分别处死各组动物,并分离各组髂动脉,置于10%中性福尔马林中固定,作HE染色。结果模型组TC、TG水平均明显升高(P<0.05),髂动脉管壁明显增厚,中膜平滑肌细胞增生,管腔内有较典型的动脉粥样斑块。结论球囊损伤及高脂喂养 VD3可成功建立大鼠动脉粥样硬化模型。     

橙皮苷对载脂蛋白E基因敲除小鼠动脉粥样硬化斑块形成的影响

目的研究橙皮苷对ApoE~(-/-)小鼠AS斑块形成的影响。方法 10周龄的雄性ApoE~(-/-)小鼠,分为对照组(ApoE~(-/-))和橙皮苷给药组(ApoE~(-/-)+HES-100mg/kg/d),每组10只,所有小鼠喂饲高脂饲料14周后收集各组织样本。采用酶学试剂盒检测各组的血脂(TC、TG、LDL-C);采用油红O染色观察各组全血管及主动脉根部的斑块面积及斑块分布;采用HE染色观察各组主动脉根部病理形态学变化。结果高脂饲料喂养ApoE~(-/-)小鼠14周后,两组之间体重无明显差异,橙皮苷给药组的总胆固醇(TC)和甘油三酯(TG)明显低于对照小鼠(P0.05);同时橙皮苷给药组的LDL-C明显小于对照组小鼠(P0.001);全血管和主动脉根部油红O染色结果表明橙皮苷减少了AS斑块面积(P0.001,P0.01);对照组斑块有大量泡沫细胞及炎症细胞形成,并伴有胆固醇结晶,发生脂纹期病变和纤维期病变,而橙皮苷能降低斑块中的炎性细胞和纤维成分,没有胆固醇结晶,多为脂纹期病变。结论橙皮苷能抑制ApoE~(-/-)小鼠AS斑块形成。     

他汀类药物治疗动脉粥样硬化的作用机制

他汀类药物是一种降胆固醇药物,随着临床的广泛应用,它的降脂效果已经得到了肯定。此外,他汀类药物对动脉粥样硬化为主的心血管疾病的治疗还包括改善血管内皮功能、抑制血管平滑肌细胞增生和迁移、维持粥样斑块的稳定性,以及抑制泡沫细胞的形成。它的这种多效性使其在心血管疾病治疗中处于越来越重要的地位。     

阿托伐他汀钙治疗颈动脉粥样硬化疗效观察

目的探讨阿托伐他汀钙对颈动脉粥样硬化的治疗效果。方法选择45例经多普勒超声检查发现颈动脉粥样硬化患者,口服阿托伐他汀钙20mg/d,疗程12个月,对比治疗前后颈动脉粥样斑块面积以及内膜中层厚度(IMT)变化。结果治疗后颈部彩色多普勒检查显示颈部动脉粥样硬化斑块面积明显减少,颈动脉内膜中层厚度有所变薄,统计学分析具有明显统计学意义。结论阿托伐他汀钙具有调节血脂及抗动脉粥样硬化的作用,可以减轻或消除缺血性脑卒中患者的颈动脉粥样硬化斑块,延缓和逆转颈动脉粥样硬化进程。     

能谱CT对颈椎动脉狭窄介入术前及术后的评估

目的:利用能谱CT彩色编码阈值软件,分析颈椎动脉硬化斑块性质及狭窄程度,评价介入支架置入术的可行性,并随访观察术后发生再狭窄的程度.方法:回顾性分析我院64例同时行头颈CTA和DSA支架置入术的患者,利用彩色编码阈值软件对所有患者颈椎动脉狭窄处进行斑块性质分析,记录狭窄程度,软硬斑块面积百分比,结合随访CTA图像观察再狭窄情况.统计分析CTA与DSA对狭窄诊断的符合率及准确率,斑块性质与狭窄的相关性.结果:(1)64例患者经过CTA检查发现68根血管不同程度狭窄或闭塞,其中动脉闭塞3例(4.4%),重度狭窄47例(69.1%),中度狭窄18例(26.5%).以DSA为标准诊断符合率为97.1%,重度狭窄及闭塞诊断准确率为100%.(2)颈椎动脉中度及重度狭窄由钙化斑块和以钙化为主的混合斑块所致61例(89.7%),二者存在相关性(χ2=21.25 P<0.05).(3)混合斑块(以钙化为主)及软斑块面积百分比大于50%的31例中,中度狭窄4例,重度狭窄27例.术后再狭窄9例(29%),二者存在相关性(χ2=12.67 P<0.05).结论:通过能谱C T彩色编码阈值软件对引起颈椎动脉狭窄的斑块性质及狭窄程度的分析,可以为介入治疗提供术前参考,并可进行随访观察.     

缓释烟酸与阿托伐他汀联合治疗颈动脉粥样硬化的疗效观察

目的研究烟酸缓释片联合阿托伐他汀对颈动脉粥样硬化的治疗效果。方法76例颈动脉粥样硬化患者随机分为两组:(1)对照组(38例),给予阿托伐他汀10mg/d;(2)治疗组(38例),给予阿托伐他汀10mg/d和烟酸缓释片1000mg/d。比较治疗前后两组血清总胆固醇(TC)、血清甘油三酯(TG)、血清低密度脂蛋白(LDL-C)和高密度脂蛋白(HDL-C)水平的改变;颈总动脉内膜-中层厚度(IMT)、颈动脉斑块厚度(Tmax)、颈动脉斑块面积(Smax)变化。结果(1)经过6个月治疗,两组TC、TG、LDL-C均有明显下降(P<0.05),但治疗组较对照组下降更显著(P<0.001)。治疗组血清高密度脂蛋白(HDL-C)升高20.7%,对照组无明显变化。(2)治疗后,治疗组的IMT、Tmax、Smax较治疗前明显下降,而对照组较治疗前无明显变化(P>0.05)。结论烟酸缓释片联合阿托伐他汀治疗颈动脉粥样疗效较单独使用阿托伐他汀好,且具有良好的安全性和耐受性。     

前循环缺血TIA患者动脉粥样硬化斑块与狭窄分析

目的探讨前循环缺血所致TIA患者颈内动脉粥样硬化斑块部位、性质、大小及动脉狭窄度。方法先以二维方法显示颈动脉(CCA)远端、分叉部(BIF)及颈内动脉(ICA)起始部的横轴、纵轴的实时二维图像及粥样硬化斑块的部位、性质、大小及动脉狭窄度,然后以Doppler方法检测收缩期血流峰值速度(PSV)、舒张末期血流速度(EDV)、阻力指数(RI)。结果本组粥样动脉硬化斑块以扁平斑为最多见,其次为硬斑与溃疡斑。结论前循环缺血患者颈内动脉粥样硬化斑块的形成、变化及管腔狭窄是导致TIA的重要原因,而中年以上、高血压、吸烟则可能是动脉粥样硬化斑块的易患因素。     

胰岛素抵抗、高胰岛素血症与高血压

探讨胰岛素抵抗(IR)、高胰岛素血症(HIS)与高血压的关系,了解IR、HIS对脂肪、葡萄糖、蛋白质代谢的影响,导致动脉壁胆固醇合成增加,使血管壁强性减弱、血管平滑肌舒缩功能失调、外调阻力增高。     

Distribution of the molecular species of phospholipids in human umbilical cord blood

The composition of phosphatidylcholine (PC) and sphingomyelin (SM) was studied in cord blood lipoproteins to determine whether equilibration of the molecular species of phospholipids among lipoproteins was comparable with that reported for adults. The molecular species distributions of PC in low density lipoprotein (LDL) differed from that of high density lipoprotein (HDL). Whereas LDL PC was richer in combinations of fatty acids with 16 and 18 carbon atoms than HDL, the HDL was markedly enriched in combinations of fatty acids with 18 and 20 carbon atoms. Sphingomyelins in LDL were richer in palmitic acid than HDL while HDL had a greater proportion of long chain sphingomyelin than LDL. The molecular species of PC and SM do not equilibrate in cord blood. The results for the SM distributions were similar to other reports for adult human lipoprotein. However, the marked differential distribution of PC among lipoproteins appears unique to cord blood. The mechanisms responsible for equilibrating PC among lipoproteins are less well developed in the neonate when compared with the adult.     

l-Carnitine effects on chemical composition of plasma lipoproteins of rabbits fed with normal and high cholesterol diets

l-Carnitine plays an important role in the mitochondrial uptake of long-chain fatty acids in mammals. It has recently been shown that this compound has a marked hypo-cholesterolemic effect when used in conjunction with lipid-rich diets. The aim of this study was to investigate the effects of l-carnitine on the fatty acid composition of plasma lipoproteins in rabbits fed with different diets. Four different groups were investigated: group I (standard diet), group II (standard diet supplemented with l-carnitine at 80 mg/kg), group III (standard diet supplemented with 0.5% cholesterol), and group IV (standard diet supplemented with 0.5% cholesterol plus l-carnitine at 80 mg/kg). The feeding period was 126 d. Total plasma cholesterol was indistinguishable in groups I and II, but increased nearly 40-fold in group III. This increment was reduced by 50% in group IV. Correspondingly, total cholesterol content in lipoprotein fractions [very low density lipoprotein (VLDL), low density lipoprotein (LDL), high density lipoprotein (HDL) separated by agarose gel chromatography was the same for groups I and II, while for animals fed a cholesterol-rich diet (III) total cholesterol in VLDL+LDL increased nearly 100-fold when compared with groups I and II but, again, the increment was reduced by 50% in group IV. In contrast, total cholesterol in HDL increased only fivefold for both groups III and IV when compared with groups I and II, indicating no effects of l-carnitine on this parameter. The reduction of total cholesterol in VLDL+LDL particles in animals fed a cholesterol-rich diet plus l-carnitine was associated with a marked decrease in the ratio of cholesteryl ester to free cholesterol and a dramatic increase in their phospholipid content; opposite effects were observed for HDL. l-Carnitine induced a marked decrease in the saturated to unsaturated C₁₆+C₁₈ fatty acid ratio in cholesteryl esters associated with VLDL and LDL from animals fed with both normal and cholesterol-rich diets. The opposite effect (a large increase in the saturated to unsaturated fatty acid ratio) was observed for both cholesteryl esters and phospholipids associated with HDL in animals fed with both diets. The results suggested that the hypocholesterolemic effects of l-carnitine could be associated with increased systemic breakdown of cholesteryl esters, a probable increase in reverse cholesterol transport, and the stabilization of a phospholipid-based structure of VLDL+LDL particles.     

ApoA-I secretion by rabbit intestinal mucosa cell cultures

Lipid and apolipoprotein (apo) A-I concentrations in different density fractions of New Zealand White (NZW) and Watanabe (WHHL) rabbit plasma were studied. Aside from the low plasma apoA-I and high density lipoprotein (HDL) cholesterol levels in WHHL rabbits, the distribution of apoA-I was also different between the two rabbits. ApoA-I was concentrated in both the HDL₂ and HDL₃ fractions of NZW rabbits but was found primarily in the HDL₃ fraction of WHHL rabbits. ApoA-I secretion in these two rabbits was further studiedin vitro by using intestinal and hepatocyte cell cultures. ApoA-I secretion was highest from cultures of the duodenum and the proximal end of the jejunum; whereas, cell cultures of the distal end of the small intestine secreted very little apoA-I into the medium. Intestinal cell cultures from WHHL rabbits secreted less, but significant amounts of, apoA-I compared to that of NZW rabbits. ApoA-I was most concentrated in the density range of 1.12–1.21 (HDL₃) fraction in medium containing 10% fetal calf serum (FCS). Serum-free medium promoted apoA-I secretion by intestinal cell cultures that was mostly found in the d>1.21 (lipoprotein-deficient) fraction. Hepatocytes isolated from the same rabbits by collagenase perfusion secreted little apoA-I, and it was found only in the d>1.21 fraction. The addition of oleic acid into the culture medium with 10% FCS decreased the secretion of total apoA-I and HDL by intestinal cell cultures and increased the secretion of very low density lipoprotein (VLDL) and intermediate density lipoproteins (IDL). The results indicate that intestinal cells, not hepatocytes, are responsible for the secretion of apoA-I and HDL₃ in rabbits, and that the secretion may be regulated under different nutritional conditions.     

The influence of protein and carbohydrate type on serum and liver lipids and lipoprotein cholesterol in rabbits

The non-lipid portions of semi-synthetic diets appear to be important determinants of hypercholesterolemia and atherosclerosis in the rabbit. Serum and liver lipid concentrations were determined in rabbits which had been pair-fed various protein (casein or soy protein isolate) and carbohydrate (sucrose or dextrose) sources as part of low fat, low cholesterol, semi-synthetic diets. It was verified that caseincontaining diets render rabbits hypercholesterolemic, while soy protein caused a degree of hypocholesterolemia. Additionally, sucrose, when fed in conjunction with casein, appears to augment this hypercholesterolemic effect. The distribution of total cholesterol among lipoprotein subclasses was increased in both the intermediate density lipoprotein (IDL) (1.006–1.019 g/ml) and low density lipoprotein (LDL) (1.019–1.063 g/ml) fractions and decreased in the high density lipoprotein (HDL) (1.063–1.21 g/ml) fraction when casein is fed. Soy protein feeding caused relatively more cholesterol to appear only in the IDL fraction when compared with commercial chow fed rabbits. Reasons for these differences may involve the saturation or suppression of endogenous lipoprotein hepatic receptors.     

Lipid metabolism and tissue composition in Atlantic salmon (Salmo salar L.)—Effects of capelin oil, palm oil, and oleic acid-enriched sunflower oil as dietary lipid sources

Triplicate groups of Atlantic salmon (Salmo salar L.) were fed four diets containing different oils as the sole lipid source, i.e., capelin oil, oleic acid-enriched sunflower oil, a 1∶1 (w/w) mixture of capelin oil and oleic acid-enriched sunflower oil, and palm oil (PO). The β-oxidation capacity, protein utilization, digestibility of dietary fatty acids and fatty acid composition of lipoproteins, plasma, liver, belly flap, red and white muscle were measured. Further, the lipid class and protein levels in the lipoproteins were analyzed. The different dietary fatty acid compositions did not significantly affect protein utilization or β-oxidation capacity in red muscle. The levels of total cholesterol, triacylglycerols, and protein in very low density lipoprotein (VLDL), low density lipoprotein (LDL), high density lipoprotein (HDL), and plasma were not significantly affected by the dietary fatty acids. VLDL, LDL, and HDL fatty acid compositions were decreasingly affected by dietary fatty acid composition. Dietary fatty acid composition significantly affected both the relative fatty acid composition and the amount of fatty acids (mg fatty acid per g tissue, wet weight) in belly flap, liver, red and white muscle. Apparent digestibility of the fatty acids measured by adding yttrium oxide as inert marker, was significantly lower in fish fed the PO diet compared to the other three diets.     

Increases in hyperlipoproteinemia,disturbances in cholesterol metabolism and atherosclerosis induced by dietary restriction in rabbits fed a cholesterol-rich diet

The influence of dietary restriction on cholesterol transport and metabolism was investigated in rabbits given standard or cholesterol-rich diets (0.2 g cholesterol/kg body weight daily) eitherad libitum or with 50% caloric ration. Dietary restriction which has only a slight influence in control rabbits markedly aggravated the disturbances induced by exogenous cholesterol. With limited feeding, control rabbits presented a moderate increase in plasma cholesterol, whereas marked aggravation of hypercholesterolemia was observed in cholesterol-fed rabbits. Analysis of the lipoprotein profile showed that the excess of plasma cholesterol with the restricted cholesterol-rich diet corresponded to an increase in the concentration of very low density lipoprotein (VLDL) and low density lipoproteins (LDL) without any additional changes in the composition of these lipoproteins. No significant change appeared in the high density lipoprotein (HDL) concentration. The parameters of cholesterol metabolism were determined, from the curves of [³H] cholesterol radioactivity decrease, using a two-pool model. The increase in cholesterol turnover rate induced by the cholesterol-rich diet was accentuated by dietary restriction, whereas rabbits on standard restricted diet showed a slight decrease. The large increase in the size of both pools A and B in cholesterol-fed rabbits was even more pronounced with limited feeding. Dietary restriction induced additional accumulation of cholesterol in the aortic wall and the grade of the lesions was also aggravated.     

Effects of 2-(2,4-dimethylphenyl)indan-1,3-dione on serum lipoprotein and lipid metabolism of rodents

2-(2,4-Dimethylphenyl)indan-1,3-dione was shown to be a potent hypolipidemic agent in rodents, lowering significantly both serum cholesterol and triglyceride levels at 20 mg/kg/day. The agent in vivo inhibited the enzymatic activities of ATP-dependent citrate lyase, acetyl-CoA synthetase, cholesterol-7α-hydroxylase, acyl-CoA cholesterol acyl transferase,sn-glycerol-3-phosphate acyl transferase and phosphatidylate phosphohydrolase. Tissue lipid levels of liver and small intestine also were reduced by the agent. The rat serum lipoprotein lipid content was modulated by the drug, which should be favorable for the removable of cholesterol from peripheral tissue for conduction to the liver for clearance from the body. Low density lipoprotein (LDL) cholesterol levels were reduced after treatment, which suggests that the agent potentially reduces deposition of cholesterol in plaques. If chemotherapy for atherosclerosis is to be successful, then the high density lipoprotein (HDL) cholesterol level needs to be elevated more than 16% to 25%, the level produced by current hypolipidemic agents. 2-(2,4-Dimethylphenyl)-indan-1,3-dione offers a 75% increase in HDL cholesterol levels and a 30% reduction of LDL cholesterol levels with a suppression of de novo synthesis of lipids and a reduction of tissue cholesterol deposition.     

The effect of dietary n−3 polyunsaturated fatty acids on HDL cholesterol in Chukot residentsvs muscovites

Native Chukot Peninsula residents, in contrast to Muscovites, consume a diet rich in n−3 polyunsaturated fatty acids. This dietary peculiarity is reflected in differences in plasma lipid and apolipoprotein contents. The Chukot residents have lower contents of total cholesterol, triglyceride, LDL (low density lipoprotein) cholesterol and apolipoprotein B, but higher HDL (high density lipoprotein) cholesterol levels than do Muscovites. The apolipoprotein A-I levels were identical in both groups. A higher HDL cholesterol to apolipoprotein A-I ratio was determined in the coastline Chukot residents (0.52±0.01) than in Muscovites (0.43±0.01; p<0.01). In contrast to Muscovites, the coastline Chukot residents also had higher n−3 and lower n−6 polyunsaturated fatty acid percentages in plasma and erythrocyte lipids, and lower phosphatidylcholine and higher sphingomyelin or phosphatidylethanolamine levels in HDL_2b and HDL₃. The higher HDL cholesterol levels in the plasma of the coastline Chukot residents appears to reflect the higher cholesterol-scavenging capacity of their HDL. We conclude from this study that the regular consumption of dietary n−3 polyunsaturated fatty acids by the coastline Chukot residents decreased LDL cholesterol transfer from plasma to peripheral cells, and enhanced cholesterol efflux from cellular membranes toward HDL.     

Nonspecific and metabolic interactions between steroid hormones and human plasma lipoproteins

Previous observations demonstrated that steroid hormones associate with plasma lipoproteins. The objective of this study was to estimate the relative importance of lipoproteins as steroid hormone binding agents in comparison to sex hormone binding globulin, corticosteroid binding globulin, and albumin in both normal and hyperlipidemic human plasma. The 16 steroid hormones and related metabolites included in the study were: androstanediol, androstenediol, androstenedione, androsterone, corticosterone, cortisol, dehydroepiandrosterone, deoxycorticosterone, dihydrotestosterone, estradiol, estriol, estrone, 17α-hydroxyprogesterone, pregnenolone, progesterone, and testosterone. The binding activity of these 16 steroid hormones with purified high density lipoprotein (HDL), low density lipoprotein and very low density lipoprotein were separately evaluated by equilibrium dialysis incubations to yield 48 steroid hormone-lipoprotein combinations for further study. In incubations with HDL, six steroid hormones (androstenediol, dehydroepiandrosterone, dihydrotestosterone, estradiol, pregnenolone, and progesterone) were identified as non-equilibrium, apparently due to metabolic conversion of the steroid hormones. The metabolic activity for the three Δ⁵-3β hydroxy steroids and estradiol appears to be fatty acid esterification by lecithin:cholesterol acyltransferase. The computer program TRANSPORT, which was used to evaluate only the nonspecific steroid hormone-lipoprotein association levels in a 16×6 matrix at simultaneous equilibrium, indicated that lipoprotein-bound steroid hormones ranged from 1% for cortisol to 56% for pregnenolone in normal human blood. Simulated projections of the increase in nonspecific steroid hormone association with lipoproteins during hyperlipidemia are also presented. These results demonstrate how lipoproteins are likely to be important in the transport and metabolism of steroid hormones in human plasma.